Article
Genetics & Heredity
Tadashi Shiohama, Katsunori Fujii, Rika Kosaki, Yoshimi Watanabe, Tomoko Uchida, Sho Hagiwara, Kaori Kinoshita, Katsuo Sugita, Yoko Aoki, Naoki Shimojo
Summary: Cardio-facio-cutaneous syndrome (CFC) is a congenital disease associated with constitutive activation of the Raf/MEK/ERK signaling cascade. This study reports severe neuroglycopenic symptoms in two children with CFC and identifies brain lesions through magnetic resonance imaging.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Genetics & Heredity
Katherine A. Rauen, Yoshiko Maeda, Alena Egense, William E. Tidyman
Summary: Cardio-facio-cutaneous syndrome (CFC) is a genetic disorder caused by germline mutations that activate the Ras/MAPK pathway, resulting in various congenital anomalies. Pathogenic variants in BRAF, MEK1, and MEK2 can lead to CFC, with the first identified vertically transmitted functional BRAF pathogenic variant found in this study.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Review
Genetics & Heredity
Xiaoao Dong, Nicholas C. Y. Png, Marielle V. Fortier, Jiin Ying Lim, Kenneth P. L. Wong, Jonathan T. L. Choo, Ene Choo Tan, Saumya Shekhar Jamuar
Summary: CFC syndrome is a rare genetic condition caused mainly by mutations in the BRAF gene and rarely by mutations in the KRAS gene. It is characterized by cardiac abnormalities, craniofacial dysmorphism, and cutaneous abnormalities. This study reports a case of symmetrical polyostotic fibrous dysplasia (FD) in a patient with CFC syndrome, suggesting a possible new clinical feature.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Angie C. Jelin, Amanda Mahle, Susan H. Tran, Teresa N. Sparks, Katherine A. Rauen
Summary: The study systematically describes the prenatal phenotype, obstetrical and neonatal outcomes of the RASopathy CFC syndrome. By analyzing the medical history data of children with CFC, it is found that there are various maternal characteristics, pregnancy complications, and prenatal and birth abnormalities. These findings contribute to better prenatal prognostic counseling and outcomes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Pediatrics
Aleksandra Szczawinska-Poplonyk, Natalia Poplonyk, Marek Niedziela, Anna Sowinska-Seidler, Pawel Sztromwasser, Aleksander Jamsheer, Monika Obara-Moszynska
Summary: Cardio-facio-cutaneous syndrome (CFCS) is a clinical disorder characterized by disruptions in the RAS/MAPK signaling pathway. This study reports a patient with CFCS who also showed immunodeficiency and growth hormone deficiency. Using whole genome sequencing, a novel pathogenic variant in the MAP2K1 gene was identified. Replacement immunoglobulin therapy and timely antibiotic prophylaxis were effective in the treatment of this patient.
FRONTIERS IN PEDIATRICS
(2022)
Article
Pediatrics
B. Ciacchini, G. Di Nardo, M. Marin, E. Borali, M. Caraccia, R. Mogni, F. Cairello, I. Rabbone, G. B. Ferrero, A. Pini Prato, E. Felici
Summary: This report describes a case of cardio-facio-cutaneous syndrome, a rare genetic disorder, characterized by craniofacial, dermatologic and cardiac defects. The patient experienced severe feeding difficulties, which led to growth arrest and malnutrition. Treatment including nasogastric tube placement and laparoscopic surgeries improved the patient's condition.
FRONTIERS IN PEDIATRICS
(2023)
Review
Endocrinology & Metabolism
Anna Papadopoulou, Evangelia Bountouvi
Summary: Noonan, Costello, and Cardio-facio-cutaneous syndromes are RASopathies characterized by overlapping clinical features and abnormalities in the Ras/MAPK signaling pathway. Skeletal dysmorphisms, including chest wall anomalies, scoliosis, and short stature, are common in affected individuals. Molecular defects in this pathway may impact bone homeostasis and create potential targets for pharmaceutical intervention.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Victorya Zakharova, Elena Raykina, Irina Mersiyanova, Ekaterina Deordieva, Dmitry Pershin, Victorya Vedmedskia, Yulia Rodina, Natalia Kuzmenko, Michael Maschan, Anna Shcherbina
Summary: RASopathies are disorders caused by germline mutations in genes that encode components of the RAS/MAPK pathway. These disorders are characterized by developmental delay, facial dysmorphisms, organ defects, and increased cancer susceptibility. This study reports a case of RASopathy caused by a cancer-associated MAP2K1 mutation, which is of postzygotic mosaic nature and may explain the patient's survival.
Article
Genetics & Heredity
Emanuele Crincoli, Chiara Leoni, Germana Viscogliosi, Roberta Onesimo, Roberta Mattei, Marco Tartaglia, Fiammetta Catania, Stanislao Rizzo, Giuseppe Zampino, Annabella Salerni
Summary: Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder caused by upregulated RAS/MAPK signaling. This study investigates the prevalence of ophthalmologic abnormalities in CFCS patients and explores genotype-endophenotype correlations. The findings suggest that CFCS patients with BRAF mutations have a higher risk of visual impairment and refractive errors, while patients with mutations in other genes have a higher prevalence of myopia. Pale optic disc is associated with specific eye muscle abnormalities. Early ophthalmologic referral is recommended for CFCS patients, especially those with BRAF mutations, due to the high risk of amblyopia.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Chiara Leoni, Domenico Marco Romeo, Michele Pelliccioni, Mariangela Di Gia, Roberta Onesimo, Valentina Giorgio, Elisabetta Flex, Marta Tedesco, Marco Tartaglia, Donato Rigante, Antonio Valassina, Giuseppe Zampino
Summary: Orthopedic manifestations are common in patients with Costello syndrome and cardio-facio-cutaneous syndrome, with differences in severity and characteristics based on genetic variants. Functional assessments by using 6MWT and PODCI could help evaluate the impact on patient outcomes and guide tailored treatment approaches.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Physiology
Kyaw Min Soe, Takuya Ogawa, Keiji Moriyama
Summary: Mutations in BCOR may lead to hyperactive root formation in OFCD syndrome by regulating ZFPM2 expression via BCL6, providing insights into the mechanism controlling root length.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Genetics & Heredity
Chiara Leoni, Germana Viscogliosi, Roberta Onesimo, Cristian Bisanti, Miriam Massese, Valentina Giorgio, Fabio Corbo, Marta Tedesco, Anna Acampora, Clelia Cipolla, Claudia Dell'Atti, Elisabetta Flex, Jacopo Gervasoni, Aniello Primiano, Donato Rigante, Marco Tartaglia, Giuseppe Zampino
Summary: CFCS is characterized by decreased bone mineral density, with BMD z-scores and t-scores below the reference range. Monitoring bone health is crucial for affected individuals.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Medicine, General & Internal
Alessandro Nepote, Gianluca Avallone, Simone Ribero, Francesco Cavallo, Gabriele Roccuzzo, Luca Mastorino, Claudio Conforti, Luca Paruzzo, Stefano Poletto, Fabrizio Carnevale Schianca, Pietro Quaglino, Massimo Aglietta
Summary: About 50% of melanomas have a BRAF mutation, with 10% of these having a V600K mutation. No specific studies have been conducted to establish a clinical and therapeutic gold standard for V600K melanoma patients. However, recent findings suggest that V600K melanoma is less dependent on the ERK/MAPK pathway and can be effectively treated with BRAF and MEK inhibitors or anti-checkpoint blockades. Nonetheless, V600K melanoma remains a medical need and is associated with poor prognosis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pediatrics
Gregorio Serra, Sofia Felice, Vincenzo Antona, Maria Rita Di Pace, Mario Giuffre, Ettore Piro, Giovanni Corsello
Summary: Cardio-facio-cutaneous syndrome (CFCS) is a rare syndrome caused by mutations in genes of the RAS/MAPK pathway. It is characterized by facial dysmorphisms, growth failure, heart defects, developmental delay, and ectodermal abnormalities. The 19p13.3 microdeletion, including the MAP 2 K2 gene, has been associated with a more severe phenotype in CFCS patients.
ITALIAN JOURNAL OF PEDIATRICS
(2022)
Review
Oncology
Sarah Zhou, Daniel Sikorski, Honghao Xu, Andrei Zubarev, May Chergui, Francois Lagace, Wilson H. Miller, Margaret Redpath, Stephanie Ghazal, Marcus O. Butler, Teresa M. Petrella, Joel Claveau, Carolyn Nessim, Thomas G. Salopek, Robert Gniadecki, Ivan V. Litvinov
Summary: Reflex molecular testing plays a crucial role in advanced melanoma patients, enabling prompt initiation of treatment and potentially improving survival outcomes. Testing for BRAF mutations is essential in predicting treatment response and guiding therapy decisions.
Biographical-Item
Genetics & Heredity
Elizabeth I. Pierpont, Susan A. Berry, Angela E. Lin, Jamie L. Lohr, Lisa A. Schimmenti, William B. Dobyns
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Pediatrics
David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani
Summary: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.
JOURNAL OF PEDIATRICS
(2021)
Article
Genetics & Heredity
Elizabeth I. Pierpont, Jill H. Simmons, Katherine J. Spurlock, Ryan Shanley, Kyriakie M. Sarafoglou
Summary: Children with HPP are at increased risk for ADHD symptoms and other behavioral health challenges, which are often under-recognized in clinical practice. Approximately 67% of children with HPP exhibit clinically significant behavioral health challenges, such as sleep disturbance and symptoms of ADHD, which are associated with reduced physical and psychosocial quality of life. Despite age-typical development of adaptive skills in most children, emotional and behavioral challenges are linked to weaker adaptive function.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Nishitha R. Pillai, Dana Miller, Elizabeth I. Pierpont, Susan A. Berry, Anjali Aggarwal
Summary: Cobalamin J disease (CblJ) is an extremely rare genetic disorder characterized by metabolic disturbances and diverse clinical symptoms. Early detection and treatment can help patients remain asymptomatic with normal growth and neurodevelopmental function.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Endocrinology & Metabolism
Ashish O. Gupta, David R. Nascene, Ryan Shanley, Daniel L. Kenney-Jung, Julie B. Eisengart, Troy C. Lund, Paul J. Orchard, Elizabeth Pierpont
Summary: The study compared outcomes after hematopoietic cell transplantation (HCT) in pediatric patients with frontal lesions versus parieto-occipital lesions in childhood cerebral adrenoleukodystrophy (cALD). It found similar rates of transplant complications and disease advancement, but a higher prevalence of psychiatric problems in patients with frontal lesions, indicating a need for comprehensive care that addresses psychiatric needs.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Clinical Neurology
Allison M. H. Foy, Rebekah L. Hudock, Ryan Shanley, Elizabeth Pierpont
Summary: This study compared different aspects of social behavior between children with RASopathies and idiopathic ASD. It found that children with RASopathies demonstrated more resilience in empathy compared to their overall social competence. The psychological factors that predicted social behavior were similar and different in these two groups. Stronger communication skills and fewer hyperactive-impulsive behaviors were associated with increased empathy and social competence in both groups. Greater emotional challenges were associated with lower social competence in children with RASopathies and stronger empathy in children with idiopathic ASD. Among children with both RASopathy and ASD, socially empathetic behaviors were observed more often. The findings highlight the distinct pattern of strengths and weaknesses in social behavior development among children with RASopathies and the importance of targeted intervention.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Article
Genetics & Heredity
Maria Kontaridis, Amy E. Roberts, Lisa Schill, Lisa Schoyer, Beth Stronach, Gregor Andelfinger, Yoko Aoki, Marni E. Axelrad, Annette Bakker, Anton M. Bennett, Alberto Broniscer, Pau Castel, Caitlin A. Chang, Lukas Cyganek, Tirtha K. Das, Jeroen den Hertog, Emilia Galperin, Shruti Garg, Bruce D. Gelb, Kristiana Gordon, Tamar Green, Karen W. Gripp, Maxim Itkin, Maija Kiuru, Bruce R. Korf, Jeff R. Livingstone, Alejandro Lopez-Juarez, Pilar L. Magoulas, Sahar Mansour, Theresa Milner, Elisabeth Parker, Elizabeth Pierpont, Kevin Plouffe, Katherine A. Rauen, Suma P. Shankar, Shane B. Smith, David A. Stevenson, Marco Tartaglia, Richard Van, Morgan E. Wagner, Stephanie M. Ware, Martin Zenker
Summary: RASopathies are a group of genetic disorders caused by genes affecting the Ras/MAPK signaling pathway. Progress has been made in translating research findings to the clinic, with the use of pathway inhibitors for treatment. The seventh International RASopathies Symposium aimed to enhance new discoveries in the field and bring together stakeholders from various backgrounds.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Elizabeth Pierpont, Daniel L. Kenney-Jung, Ryan Shanley, Abigail L. Zatkalik, Ashley E. Whitmarsh, Samuel J. Kroening, Amy E. Roberts, Martin Zenker
Summary: This study evaluated the neurological and neurodevelopmental features of patients with CFC syndrome and found that gene variants were associated with abnormal EEGs and neurodevelopmental impairments.
GENETICS IN MEDICINE
(2022)
Review
Biotechnology & Applied Microbiology
Ashish O. Gupta, Gerald Raymond, Elizabeth Pierpont, Stephan Kemp, R. Scott McIvor, Arpana Rayannavar, Bradley Miller, Troy C. Lund, Paul J. Orchard
Summary: Adrenoleukodystrophy (ALD) is a rare disorder that causes severe neuroinflammation and fatality. Historically, allogeneic hematopoietic stem cell transplantation (HSCT) has been the only therapeutic option to halt the progression of cerebral ALD. However, recent studies have explored lentiviral-based gene therapy as an alternative treatment.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Article
Genetics & Heredity
Daniel. L. L. Kenney-Jung, Dante. J. J. Rogers, Samuel. J. J. Kroening, Abigail. L. L. Zatkalik, Ashley. E. E. Whitmarsh, Amy. E. E. Roberts, Martin Zenker, Maria Luigia Gambardella, Ilaria Contaldo, Chiara Leoni, Roberta Onesimo, Giuseppe Zampino, Marco Tartaglia, Domenica. I. I. Battaglia, Elizabeth. I. I. Pierpont
Summary: Gene variants affecting the RAS-MAPK pathway can cause CFCS, a multi-system disorder, with IESS being a serious complication. In this study, it was found that IESS occurred in 10% of CFCS patients, with most cases associated with BRAF variants. The onset of spasms occurred at a median age of 5.4 months and most patients required anti-seizure medication for treatment. Patients with a history of IESS had limited neurodevelopmental outcomes and were more likely to develop other types of epilepsy.
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2022)
Review
Endocrinology & Metabolism
Elizabeth I. Pierpont, Ashley R. Isaia, Erin McCoy, Sarah J. Brown, Ashish O. Gupta, Julie B. Eisengart
Summary: X-linked adrenoleukodystrophy (ALD) is a rare inherited neurological disorder that presents challenges for clinical management. This comprehensive review synthesizes current knowledge about the neurocognitive and mental health effects of ALD, providing context for improved patient care. The results highlight predictive factors and brain-behavior relationships associated with the diverse manifestations of ALD, while also identifying gaps for future research.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Editorial Material
Clinical Neurology
Elizabeth I. Pierpont
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Genetics & Heredity
Daniel L. Kenney-Jung, Josue E. Collazo-Lopez, Dante J. Rogers, Ryan Shanley, Abigail L. Zatkalik, Ashley E. Whitmarsh, Amy E. Roberts, Martin Zenker, Elizabeth I. Pierpont
Summary: This study analyzed the clinical characteristics of epilepsy and response to anti-seizure medications in patients with cardiofaciocutaneous syndrome. The results showed that many patients were unable to achieve adequate seizure control despite the use of multiple medications, suggesting a need for better treatment options.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Elizabeth I. Pierpont, Anton M. Bennett, Lisa Schoyer, Beth Stronach, April Anschutz, Sarah C. Borrie, Benjamin Briggs, Emma Burkitt-Wright, Pau Castel, Ion C. Cirstea, Fieke Draaisma, Michelle Ellis, Vanessa S. Fear, Megan N. Frone, Elisabetta Flex, Bruce D. Gelb, Tamar Green, Karen W. Gripp, Sattar Khoshkhoo, Mark W. Kieran, Karolin Kleemann, Bonita P. Klein-Tasman, Maria I. Kontaridis, Paul Kruszka, Chiara Leoni, Clifford Z. Liu, Nadia Merchant, Pilar L. Magoulas, Christopher Moertel, Carlos E. Prada, Katherine A. Rauen, Renee Roelofs, Rodrigue Rossignol, Christine Sevilla, Gigi Sevilla, Ryan Sheedy, Elliot Stieglitz, Daochun Sun, Dagmar Tiemens, Forest White, Ellen Wingbermuehle, Cordula Wolf, Martin Zenker, Gregor Andelfinger
Summary: Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are responsible for RASopathies, a group of genetically overlapping syndromes characterized by distinct facial features, short stature, cancer predisposition, and anomalies in major body systems. The 8th International RASopathies Symposium focused on global perspectives in clinical care and research, aiming to foster international collaborations and diverse patient cohorts for interventional trials.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Endocrinology & Metabolism
Rebecca E. Wiersma, Ashish O. Gupta, Troy C. Lund, Kyriakie Sarafoglou, Elizabeth Pierpont, Paul J. Orchard, Bradley S. Miller
Summary: Primary adrenal insufficiency (PAI) is often the initial manifestation of X-linked adrenoleukodystrophy (X-ALD), and early identification of X-ALD is critical for timely intervention. Plasma very long chain fatty acid testing should be performed in all boys with PAI to ensure the diagnosis of X-ALD.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)